Extending survival with innovations in multiple myeloma therapy

Although more than 160,000 people in the United States are living with multiple myeloma, many people have never heard of the disease until they are diagnosed, says Alfred L. Garfall, MD. “But I explain to them that even though they haven’t heard of myeloma before, it’s actually one of the biggest success stories in oncology.” Dr. Garfall is the Section Chief of Myeloma and Director of Autologous Hematopoietic Stem Cell Transplantation in Hematology-Oncology at Penn Medicine.

In the United States, the five-year relative survival rate for multiple myeloma is 62.4 percent, according to the National Cancer Institute. That’s a marked increase from 2000 to 2004, when five-year relative survival was just 37.7 percent. Although myeloma is still considered incurable, it is highly treatable. “Over the last decade, there’s been a steady development of new therapies for managing this disease,” says Dr. Garfall. “The more therapies you can get your hands on, the longer you’ll live.”

The growing complexity of multiple myeloma treatment

Multiple myeloma is a clinically heterogeneous plasma cell malignancy that requires individualized, long-term management, says Shivani Kapur, MD, Assistant Professor of Clinical Medicine in Hematology-Oncology at Penn Medicine. Disease presentation and clinical course can vary widely based on diverse cytogenetic risk profiles, patterns of organ involvement, and treatment tolerability considerations. At diagnosis, patients may present with constitutional symptoms, cytopenias, lytic bone disease, recurrent infections, or renal failure.

Despite that heterogeneity, most newly diagnosed patients receive induction with multi-agent combination therapy. The typical quadruplet induction therapy generally includes an anti-CD38 antibody, a proteasome inhibitor, an immunomodulatory drug, and dexamethasone. Transplant-eligible patients then receive an autologous stem cell transplant for consolidation, followed by maintenance therapy tailored to cytogenetic risk and tolerability.

When patients relapse, their prior exposure, disease biology, and patient fitness help guide treatment selection, with options including CAR T cell therapy, bispecific antibodies, and novel combinations. As treatment options have expanded, decision-making has become more individualized.

“All of oncology has gotten more complex over time, and blood cancers are no exception. But as more and more treatment options have become available for myeloma, we have also learned how to personalize those treatments for each patient,” notes Dr. Garfall. “Because we see such a high volume of patients with this disease, and have subspecialized providers focused on this one narrow area, we have the expertise to take a more nuanced approach to treatment.”

Advances in immunotherapy: CAR T therapy, bispecific antibodies, and clinical trials

Many of the recent advances in myeloma have been in the immunotherapy space, including FDA-approved CAR T cell therapy. Bispecific antibodies—which redirect a patient’s T cells to target myeloma cells—are another important class of modern therapy. “We have four FDA-approved bispecific antibodies initially approved for relapsed disease, and which are likely very shortly to be approved as part of second-line therapy,” Dr. Garfall says.

Penn Medicine was one of the leading sites for clinical trials that led to the approval of the bispecific antibody teclistamab, and is now involved in various other trials to explore new approaches to using the drug. In the ongoing phase III MajesTEC-4 study, for example, researchers are studying teclistamab as part of maintenance therapy for myeloma patients following an autologous stem cell transplant. Preliminary results are promising, Dr. Garfall says, with high rates of minimal residual disease (MRD)-negative complete response in patients taking teclistamab.

Meanwhile, Dr. Garfall is the principal investigator of a study that will investigate a new way to dose teclistamab in patients with relapsed or refractory myeloma. The drug was initially studied as a continuous long-term therapy, but research suggests that a short course may be similarly effective, while reducing the risk of complications from immune suppression.

In this study, researchers will compare long-term teclistamab therapy with limited courses of teclistamab lasting six to nine months. “We’re hopeful this could be a more patient-friendly way to give patients with relapsed myeloma a break from treatment and the burdens of supportive care,” says Dr. Garfall.

As with all anti-oncogenic agents, safety is a concern with teclistamab. Patients taking the agent often receive supportive care such as preventive antibiotics to mitigate the risk of infection. They also receive infusions of antibodies, since teclistamab blocks the ability to produce antibodies.

Other studies are also underway to explore new targeted therapies, new approaches to CAR T therapy, and a new class of drugs, trispecific antibodies, which aim to advance the concept of bispecific antibodies.

Multiple myeloma treatment at Penn Medicine

Myeloma is a lifelong illness, so it’s important for patients to develop a relationship with a local care team who can provide treatment close to home. Because the initial quadruplet drug regimen is standard for most newly diagnosed patients, and prompt treatment is essential, it often makes sense for patients to start therapy in their communities. But there are benefits for patients and providers to connect with the myeloma team at Penn Medicine, who can consult on next steps, including eventual cell therapies or other treatments as the disease progresses.

Dr. Kapur, who is herself a noted clinical researcher in myeloma, observes that advances in myeloma are coming at a fast pace, with a consequent improvement in understanding the disease. “Referring patients for evaluation at Penn Medicine early in their myeloma treatment helps us formulate a precise plan that may include new therapies or clinical trials,” she says.

In addition to its large group of myeloma specialists, the Penn Medicine Division of Hematology and Oncology stands out for its multidisciplinary approach. “We have an experienced team and a lot of cross-disciplinary collaboration, making it easy to consult with other specialists to manage complicated cases,” Dr. Kapur says, adding that this commitment to collaboration extends to referring physicians. “Our goal is to make things as convenient as possible for patients while still providing them with access to every possible treatment option.”

Referrals and consultations

To refer a patient to the Penn Medicine Division of Hematology and Oncology, please call 877-937-7366 or refer a patient online.